Nucleus incertus corticotrophin‐releasing factor 1 receptor signalling regulates alcohol seeking in rats. (20th July 2016)

• Record Type: Journal Article
• Authors: Walker, Leigh C.; Kastman, Hanna E.; Koeleman, Jan A.; Smith, Craig M.; Perry, Christina J.; Krstew, Elena V.; Gundlach, Andrew L.; Lawrence, Andrew J.
• Is Part Of: Addiction biology. Volume 22:Number 6(2017)
• Page Start: 1641
• Page End: 1654
• Publication Date: 2016-07-20
• Subjects: alcohol -- corticotrophin‐releasing factor -- nucleus incertus -- reinstatement -- relaxin‐3 -- stress; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12426
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: Alcoholism is a chronic relapsing disorder, and stress is a key precipitant of relapse. The nucleus incertus (NI) is highly responsive to corticotrophin‐releasing factor (CRF) and psychological stressors, receives a CRF innervation and expresses CRF1 and CRF2 receptor mRNA. Furthermore, the ascending NI relaxin‐3 system is implicated in alcohol seeking in rats. Therefore, in alcohol‐preferring rats, we examined the effect of bilateral injections into the NI of the CRF1 receptor antagonist, CP376395 or the CRF2 receptor antagonist, astressin‐2B on yohimbine‐induced reinstatement of alcohol seeking. Using quantitative PCR analysis of NI micropunches, we assessed the effects of chronic alcohol consumption on gene expression profiles for components of the relaxin‐3 and CRF systems. Bilateral intra‐NI injections of CP376395 (500 ng/0.25 µl) attenuated yohimbine‐induced reinstatement of alcohol seeking. In contrast, intra‐NI injections of astressin‐2B (200 ng/0.25 µl) had no significant effect. In line with these data, CRF1, but not CRF2, receptor mRNA was upregulated in the NI following chronic ethanol intake. Relaxin family peptide 3 receptor mRNA was also increased in the NI following chronic ethanol. Our quantitative PCR analysis also identified CRF mRNA within the rat NI, and the existence of a newly identified population of CRF‐containing neurons was subsequently confirmed by detection of CRF immunoreactivity in rat and mouse NI. These data suggest that NI neurons contribute to reinstatement of alcohol seeking, via an involvement of CRF1 signalling. Furthermore, chronic ethanol intake leads to neuroadaptive changes in CRF and relaxin‐3 systems within rat NI. Abstract : Bilateral injections into the rat nucleus incertus (NI) of CP376395 (500 ng/0.25 µl) attenuated yohimbine‐induced reinstatement of alcohol seeking, whereas astressin‐2B (200 ng/0.25 µl) had no significant effect. CRF‐receptor 1, but not CRF‐receptor 2, mRNA was upregulated in the NI following chronic ethanol intake. Corticotrophin‐releasing factor (CRF) mRNA is expressed within the rat NI; CRF‐containing neurons were confirmed by immunohistochemistry. NI neurons apparently contribute to alcohol seeking, via CRF‐receptor 1 signaling. Chronic ethanol intake causes neuroadaptive changes in NI CRF and relaxin‐3 systems.